4/10/2015

Cystic ovaries in (dairy) cows Geert Opsomer Department of Reproduction, Obstetrics and Herd Health Faculty of Veterinary Medicine Ghent University Belgium 1

What are cystic ovaries? In cows structure >2.5 cm diameter present for >10 days ..in absence of a CL

Cystic ovaries • Incidence: – 10% (5 to 40%) – most often: 30-40 DIM and 190-220 DIM

• Economics: – increase in calving interval: 22-64 days – increase in culling (follicular cysts) – cost: 137dollar/lactation • but higher milk production? 3

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Distribution du nombre total de kystes (%) au cours du post-partum chez la vache (D’après Whitmore et al. 1974, Wiltbank et al. 1953, Whitmore et al. 1979, Erb et White 1981, Kirk et al. 1982) 30

25

20

15

10

5

0 0-15

16-30

31-45

46-60

61-75

76-90

91-105

106-120

121-135

136-150

>150

2003-2004

Risk factors • high milk production – genotype/phenotype

• • • •

season (winter-summer) higher parity puerperal disease nutrition: NEB-phyto-oestrogens-β-carotene

5

Symptoms • anoestrus • nymphomania • irregular cyclicity (accuracy of heat detection?)

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Types of cysts • Benign – cystic corpus luteum: normal CL with internal cyst (cavity) – follicular cyst ‘diagnosed per accident’:

• Pathologic – follicular cyst: thin wall - produces estradiol – can be luteinized by GnRH – does not respond to PG – luteal cyst: thick walled (>3 mm) – produces progesterone – regresses following PG injection 8

Diagnosis • rectal palpation and ultrasound • measurement of progesterone in blood or milk

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Differential diagnosis • pathologic versus benign cyst: – anamnesis – presence of CL • follicular versus luteal: – clinical examination and hormone measurement in blood/milk • large follicle: – uterine tone • cystic corpus luteum: – diameter of cavity – wall thickness - stigma of ovulation • granulosa cell tumor: – bigger – whole ovary increased in size 10

Can cysts be diagnosed from one examination? What are the best methods of diagnosis and differentiation currently available?

Single manual examination per rectum is difficult

Out of 29 ‘cases’, repeated ultrasound revealed 15 cysts - 6 follicular - 9 luteal 3 large follicles 11 normal CL Ribadu et al, 1994

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Using a 7.5 MHz head.. Follicular Internal diameter (mm)

Wall thickness (mm)

Luteal

35-37

28-30

2.5-2.7

5 - 6

Tebble et al, 2001

40

a)

30

Hormone

P roge steron e 20

O es trad iol FS H

10

0 b)

F 1 RO

Follicle diameter (mm)

25

F 2 RO F 3 RO *

20

F 4 RO F 7 RO

15

F 9 RO F1 LO

10

F2 LO * F3 LO

5 10

20

30

40

50

60

70

80

D a ys

Noble et al, 2000

Folliculaire cysten

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2003-2004

Ch. Hanzen ULg, FMV, Les kystes ovariens chez la vache

2003-2004

Ch. Hanzen ULg, FMV, Les kystes ovariens chez la vache

2003-2004

Ch. Hanzen ULg, FMV, Les kystes ovariens chez la vache

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Polycystic ovary

2003-2004

Ch. Hanzen ULg, FMV, Les kystes ovariens chez la vache

Luteal Cyst

21

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Kyste ovarien lutéinisé après incision (0489)

2003-2004

Ch. Hanzen ULg, FMV, Les kystes ovariens chez la vache

Luteale Cyste

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Cyst and corpus luteum

26

27

(Vanholder, 2005)

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Day 14 Cystic CL

Cystic corpus luteum

Pathogenesis of COD is not completely elucidated difficult to examine: – dynamic structures – cause and effect – use of very artificial protocols to induce cysts

COD is caused by a failure to ovulate – but probably not because of a shortage of LH (even higher LH – good response to GnRH treatment) 30

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Hypothalamus GnRH

Oestradiol +

Preovulatory oestradiol-surge +

Pituitary LH

surge

FSH LH pulses

Follicle growth wave

Pre-ovulatory follicle

Selection & Deviation

Ovulation 31

Normal progesterone profile: first rise in milk progesterone (≥ ≥ 15 ng/ml milkfat) occurs before day 50 post partum and positive levels for approximately two weeks alternate with low levels for about one week progesterone ng/ml milkfat

120 105 90 75 60 45

AI

pregnant

30 15 0 0

7

14

21

28

35

42

49

56

63

70

77

84

91

98

105

112

119

126

133

140

days post partum 32

Delayed cyclicity: consistently low progesterone concentrations for at least 50 days after calving progesterone ng/ml milkfat

120 105 90 75 60 45

AI pregnant

30 15 0 0

7

14

21

28

35

42

49

56

63

70

77

84

91

98

105

112

119

126

133

140

days post partum 33

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Cessation of cyclicity: normal cyclicity is interrupted by at least 14 days of consistently low progesterone levels

progesterone ng/ml milkfat 120

105

90

75

60

45

30

15

0 0

7

14

21

28

35

42

49

56

63

70

77

84

91

98

105

112

da ys po st pa rtum

34

Prolonged luteal phase: progesterone levels remain positive for at least 20 consecutive days without a preceding insemination progesterone ng/ml milkfat

120 105 90 75 60 45

AI

pregnant

30 15 0 0

7

14

21

28

35

42

49

56

63

70

77

84

91

98

105

112

119

126

days post partum 35

Short luteal cycles: at least one luteal phase (excluding the first) which length does not exceed 10 days

120

progesterone ng/ml milkfat

105 90 75 60

pregnant 45

AI

30 15 0 0

7

14

21

28

35

42

49

56

63

70

77

84

days post partum 36

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Irregular profile: an irregular pattern not belonging to one of the other abnormalities, or showing a combination of two or more of abnormalities progesterone ng/ml milkfat 120 105 90 75 60 45 30 15 0 0

7

14

21

28

35

42

49

56

63

70

77

84

91

98

105 112 119 126 133 140 147 154 161 168 175 182 189 196 203

days post partum 37

Results of studies based on prog analysis • No. of cycles • Normal cyclical patterns (%) • Delayed cyclicity (%) • Temp cessation of cyclicity • Prolonged luteal phase (%) • Short cycles • Other irregular patterns

Traditional herds Modern high yielding herds (Fagan and (Opsomer et Roche 1986) al. 1998)

• 448 • 78 • 7 • 3 • 3 • 4 • 4

463 53 21 3 20 0,5 2,5 38

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Conclusions of studies based on progesterone profiles 1/2 • In modern high-yielding dairy cows resumption of ovarian activity is retarded • Almost half (49%) of the high-yielding dairy cows suffer from ovarian dysfunction in the pre-service p.p. period • Delayed cyclicity and prolonged luteal phase account together for 90% of all abnormalities

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Conclusions of studies based on progesterone profiles 2/2 • While insemination should be started at around 60 days after calving in order to attain the optimal calving interval of 365 days, 64% of the cows still suffer from an ovarian malfunction at that time after calving • Further epidemiological research is needed to find out risk factors for the occurrence of ovarian dysfunctions 41

Conclusions of risk factor analysis • Major risk factors for delayed cyclicity are: – clinical signs of negative energy balance: the decrease in body condition during first 60 days after calving, clincal ketosis and low milk protein concentrations

• Major risk factors for prolonged luteal cycles are: – a too early start of ovarian activity after calving – the occurrence of puerperal disorders 42

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43

44

Resumption of ovarian activity after calving Brain

LH

FSH Estradiol

OVARY

> 20%!

METABOLISM

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Effects of negative energy balance Metabolic ‘messengers’

GnRH hypothalamus

pituitary gland (hypofysis)

FSH LH Metabolic ‘messengers’ -Glucose -Ketobodies -Nefa's -Urea

ovary

LH surge Ovulation 46

Transvaginal follicular fluid aspiration

47

48

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B -h y d r o x y b u ty r a te (m M )

β-hydroxybutyrate 2,5 2

serum

1,5

follicular fluid

1 0,5 0 -7

0

11

14

20

26

33

40

46

days to partus (Leroy et al., 2004)

49

NEFA 0,6

N E F A (m M )

0,5 0,4 0,3

serum

0,2

follicular fluid

0,1 0 -7

0

11

14

20

26

33

40

46

days to partus 50

(Leroy et al., 2004)

% 35 30 25 20

serum

15 10

follicular fluid

5 0

oleic acid (C18:1)

Stearic Palmitic Linoleic acid acid acid (C18:0) (C16:0) (C18:2) 51

(Leroy , 2005)

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In vitro effect of elevated NEFA levels on proliferation of granulosa cells

48 hr

with palmitic, stearic and/or oleic acid

• fatty acids like palmitic and stearic acid have a significant negative effect on granulosa cell growth and proliferation (Vanholder, 2005) 52

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Typical features of PCOS in women showing comparisons with COD in the dairy cow (1/2) • PCOS occurs mainly in obese women • PCOS women often suffer from abnormalities in the lipid metabolism (elevated NEFA and cholesterol levels) • PCOS seems to have an heriditary background • hirsutism often occurs in PCOS women 54

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Typical features of PCOS in women showing comparisons with COD in the dairy cow (2/2) • approximately 50% of PCOS patients are insulin resistant • insulin resistance may be seen as a key factor in the pathogenesis of PCOS • insulin resistance is seen as the link between the metabolic problems and PCOS 55

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Comparable studies • O. Balogh (2003): – cows showing insulin resistance at 10 to 15 days post partum

prolonged interval calving-1st ovulation

57

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Materials and Methods 15 COD cows: – high yielding Holstein-Friesians – between 2th and 5th lactation – reproductive problems (acyclia or irregular cycles) – cystic structure on one or both ovaries (rectal palpation and ultrasound)

15 control cows: – matched according to herd, DIM, lactation number – no gynaecological problems 58

Study Design each COD cow was matched with a control cow all 30 cows were subjected to an IVGTT differences in glucose tolerance and in endogenous insulin response following a standard glucose load between COD cows and their matched controls were analyzed

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Parameter

COD (n=15)

Controls (n=15)

P

Basal glucose (mmol/l)

3.55 (2.93-3.98)

3.45 (2.63-3.89)

0.40

k (%/min)

1.65 (0.71-2.85)

1.90 (0.94-2.47)

0.23

T1/2 (min)

48.86 (24.30-97.16)

38.61 (28.05-74.08)

0.23

AUC glucose (T60) (mmol/l/55min)

507 (341-657)

463 (352-614)

0.09

AUC glucose (T120) (mmol/l/115min)

786 (555-1061)

710 (533-958)

0.12

Basal insulin (µIU/ml)

9.91 (6.2-26)

10.62 (1.8-23)

0.51

Ins peak (µIU/ml)

94 (19-195)

136 (75-240)

0.04

∆ Max (µIU/ml)

84 (13-186)

125 (57-226)

0.04

AUC insulin (T60) (µIU/ml/55min)

3066 (882-5625)

4135 (2078-6860)

0.09

AUC insulin (T120) (µIU/ml/115min)

4025 (1748-6156)

4959 (2442-7829)

0.20 60

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Results no significant differences in the glucose clearance COD cows have a significantly lower insulin response: – both the insulin peak and insulin increment are significantly lower for COD cows – this was caused by the fact that 5 of the 15 COD cows showed almost no insulin response following the glucose load 61

62

63

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Hypothalamus

Glucose

GnRH

Oestradiol

NEFA

Pituitary Preovulatory oestradiol-surge LH

surge

FSH LH pulses

COF

Insulin, leptin, IGF1glucose

NEFA

DF atresia 65

Van der Lende et al. (2004) Journal of Dairy Science

fr a c tio n d a u g h te r s w ith P c o n c e n tr a tio n s > 3 n g /m l

1.0

0.5

22

78

0.0 0

20

40

60

lactation stage (days)

80

100 66

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General conclusions 1/2 • A lot of the modern high yielding dairy cows suffer from ovarian disturbances during the immediate postpartum period • Health problems and clinical signs of a severe negative energy balance are among the most important risk factors for these postpartal ovarian disturbances 67

General conclusion 2/2 • High-yielding dairy herds need an effective transition cow program in order to prevent a lot of early postparturient problems and an impaired fertility – these programs should include: • specific adjustments for cows with a high genetic ability to produce milk (e.g. optimization of the dry matter intake) • accurate procedures to catch problem cows as soon as possible

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How to avoid insulin 'problems' • Transition cow program based on: – avoiding too fat cows at calving – stimulate dry matter intake at calving: • avoid stress around calving • avoid major changes in the ration around calving

– reduce a steep insulin drop around calving: • start with concentrates before calving • offer glucogenic rations (propylene glycol) before calving 69

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Thank you for your attention

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Treatment of COD difficult to accurately conclude from literature because: – diagnosis? – time post partum? – control group? – combination of several drugs? – definition of positive result?

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Treatment options COD self cure: – spontaneous regression of 40 to 70% 5mm: 69% preg rate

with other follicles >5mm

: 91% preg rate

Cysts - take home advice... Refine ultrasound skills Look for other structures on BOTH ovaries - CL - other follicles >5mm Discern follicular from luteal cysts Monitor both types of cyst carefully -to improve fertility indices -to reduce culling (especially follicular)

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